A principled link between object naming and representation is available to infants by seven months of age.

By their first birthdays, infants represent objects flexibly as a function of not only whether but how the objects are named. Applying the same name to a set of different objects from the same category supports object categorization, with infants encoding commonalities among objects at the expense of individuating details. In contrast, applying a distinct name to each object supports individuation, with infants encoding distinct features at the expense of categorical information. Here, we consider the development of this nuanced link between naming and representation in infants' first year. Infants at 12 months (Study 1; N = 55) and 7 months (Study 2; N = 96) participated in an online recognition memory task. All infants saw the same objects, but their recognition of these objects at test varied as a function of how they had been named. At both ages, infants successfully recognized objects that had been named with distinct labels but failed to recognize these objects when they had all been named with the same, consistent label. This new evidence demonstrates that a principled link between object naming and representation is available by 7 months, early enough to support infants as they begin mapping words to meaning.

I See What You Are Saying: Hearing Infants' Visual Attention and Social Engagement in Response to Spoken and Sign Language.

Infants are endowed with a proclivity to acquire language, whether it is presented in the auditory or visual modality. Moreover, in the first months of life, listening to language supports fundamental cognitive capacities, including infants' facility to form object categories (e.g., dogs and bottles). Recently, we have found that for English-acquiring infants as young as 4 months of age, this precocious interface between language and cognition is sufficiently broad to include not only their native spoken language (English), but also sign language (American Sign Language, ASL). In the current study, we take this work one step further, asking how "sign-naïve" infants-hearing infants with no prior exposure to sign language-deploy their attentional and social strategies in the context of episodes involving either spoken or sign language. We adopted a now-standard categorization task, presenting 4- to 6-month-old infants with a series of exemplars from a single category (e.g., dinosaurs). Each exemplar was introduced by a woman who appeared on the screen together with the object. What varied across conditions was whether this woman introduced the exemplar by speaking (English) or signing (ASL). We coded infants' visual attentional strategies and their spontaneous vocalizations during this task. Infants' division of attention and visual switches between the woman and exemplar varied as a function of language modality. In contrast, infants' spontaneous vocalizations revealed similar patterns across languages. These results, which advance our understanding of how infants allocate attentional resources and engage with communicative partners across distinct modalities, have implications for specifying our theories of language acquisition.

Construing events first-hand: Gesture viewpoints interact with speech to shape the attribution and memory of agency.

Beyond conveying objective content about objects and actions, what can co-speech iconic gestures reveal about a speaker's subjective relationship to that content? The present study explores this question by investigating how gesture viewpoints can inform a listener's construal of a speaker's agency. Forty native English speakers watched videos of an actor uttering sentences with different viewpoints-that of low agency or high agency-conveyed through both speech and gesture. Participants were asked to (1) rate the speaker's responsibility for the action described in each video (encoding task) and (2) complete a surprise memory test of the spoken sentences (recall task). For the encoding task, participants rated responsibility near ceiling when agency in speech was high, with a slight dip when accompanied by gestures of low agency. When agency in speech was low, responsibility ratings were raised markedly when accompanied by gestures of high agency. In the recall task, participants produced more incorrect recall of spoken agency when the viewpoints expressed through speech and gesture were inconsistent with one another. Our findings suggest that, beyond conveying objective content, co-speech iconic gestures can also guide listeners in gauging a speaker's agentic relationship to actions and events.

Clinical implementation of plasma EGFR T790M testing using droplet digital PCR in TKI-resistant NSCLC patients.

BACKGROUND: Majority of non-small cell lung cancer (NSCLC) patients progressed on epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) due to acquired T790M mutation. Blood sample is increasingly used in clinical setting for EGFR T790M detection and our laboratory employed the droplet digital PCR (ddPCR) methodology for testing. This study investigated the positive rate, specimen type for rebiopsy and clinical impact of blood-based EGFR T790M testing. METHODS: We retrospectively evaluated clinical samples that underwent plasma EGFR T790M testing in TTSH Molecular Diagnostic Laboratory from August 2017 to September 2019. Data on diagnosis, EGFR activating and T790M mutations, and treatment strategies were recorded. RESULTS: A total of 104 progressive NSCLC cases were included in this study. Overall, 46 patients (44.2%) were tested T790M positive, and 47.8% of these tested positive had low levels (defined as ≤3% fractional abundance and <50 copies/mL plasma), which may be missed by the conventional methods with lower sensitivity. Of these tested with low T790M abundance, 77.3% subsequently received osimertinib. Activating mutations were not detected in 42 (40.4%) cases, indicating that the tumors were not actively shedding ctDNA. Among these, 24 patients underwent repeat testing with tissue or blood specimens. Thirteen patients were subsequently tested T790M positive and 12 of them switched treatment to osimertinib. The recommendation to repeat testing with a different biopsy or after a suitable interval increased the overall positive rate to 56.7% (59/104). CONCLUSION: The use of a highly sensitive platform such as ddPCR for the detection of low abundance T790M, and the approach of repeat testing in cases with insufficient ctDNA increased the positive rate. This in turn identified more patients who are eligible for targeted therapy.

Wilms' tumor 1 silencing decreases the viability and chemoresistance of glioblastoma cells in vitro: a potential role for IGF-1R de-repression.

Wilms' tumor 1 (WT1) is a transcription factor with a multitude of downstream targets that have wide-ranging effects in non-glioma cell lines. Though its expression in glioblastomas is now well-documented, the role of WT1 in these tumors remains poorly defined. We hypothesized that WT1 functions as an oncogene to enhance glioblastoma viability and chemoresistance. WT1's role was examined by studying the effect of WT1 silencing and overexpression on DNA damage, apoptosis and cell viability. Results indicated that WT1 silencing adversely affected glioblastoma viability, at times, in synergy with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and cisplatin. To investigate other mechanisms through which WT1 could affect viability, we measured cell cycle distribution, senescence, and autophagy. WT1 silencing had no effect on these processes. Lastly, we examined WT1 regulation of IGF-1R expression. Counterintuitively, upregulation of IGF-1R was evident after WT1 silencing. In conclusion, WT1 functions as a survival factor in glioblastomas, possibly through inhibition of IGF-1R expression.

Frequency and seasonal variation of ophthalmology-related internet searches.

OBJECTIVE: To use internet search activity to reveal the intensity of public interest and seasonal variation in ophthalmology-related diseases, symptoms, and treatments. DESIGN: Time-series analysis of internet search data. METHODS: Google trend data for ophthalmology terms for the United States, the United Kingdom, Canada, and Australia from 2004 through 2008 were studied. Mean population-weighted temperature and fraction of schools in session were estimated from databases, and relative potential sunlight intensity was calculated. Multivariable linear regression was used to predict search term frequency based on environmental variables. RESULTS: Relative to diabetes searches (100%), common US eye-related searches were: "glasses" (44%), "Lasik" (16%), "contact lenses" (12.4%), "pink eye" (9.5%), "glaucoma" (5.9%), "cataract" (4.1%), "dry eyes" (2.1%), "eye twitching" (1.9%), and "eye pain" (1.9%). Seasonal nature was high for "conjunctivitis" (r(2) = 0.37), "pink eye" (r(2) = 0.32), "eye floaters" (r2 = 0.26), and "stye" (r(2) = 0.19), moderate for "glaucoma" (r(2) = 0.09) and "eye twitching" (r(2) = 0.06), and low for "uveitis" (r(2) = 0.02) and "macular degeneration" (r(2) < 0.01). Heat was associated with "stye" and cold was associated with "pink eye," "conjunctivitis," and "glaucoma" (all p < 0.002). Sunlight intensity was associated with "dry eyes" and "eye floaters" (p < 0.01). School sessions were associated positively with "eye twitching" (p >= 0.001) and negatively with "eyeglasses." "Eye allergy," "itchy eyes," and "watery eyes" were highly seasonal (r(2) = 0.75-0.38) and associated with "pollen" searches. CONCLUSIONS: Internet ophthalmology searches relate (in decreasing order) to refractive correction, eye diseases, and eye symptoms. Search study reveals the seasonality and environmental associations of interest in health terms.

Down-regulation of Wilms' tumor 1 expression in glioblastoma cells increases radiosensitivity independently of p53.

The Wilms' tumor 1 (WT1) gene is overexpressed in human glioblastoma and correlates with wild-type p53 status. In other cell types, WT1 inhibits p53-mediated apoptosis in response to DNA damaging agents. However, neither this interaction nor the relationship between WT1 and radiosensitivity has been studied in glioblastoma. To study this interaction, we generated LN-229 glioma cell lines (p53 mutant) stably expressing WT1 isoforms and induced apoptosis by transfecting with different doses of wild-type p53 plasmid expression vector. Constitutive expression of WT1 did not protect against exogenous p53-mediated apoptosis. Likewise, WT1 expression did not protect against endogenous p53-mediated cell death induced by radiotherapy in U87MG cells, which contain functional wild-type p53. We then tested the efficacy of WT1 siRNA in inhibiting WT1 expression and its effect on radiosensitivity. In T98G and LN-18 glioma cells, which possess p53 mutations, WT1 siRNA decreased WT1 protein to almost undetectable levels by 96-h post-transfection. Furthermore, WT1 siRNA transfection caused a significantly larger decrease in viability following irradiation than was seen in untransfected cells in both cell lines after treatment with ED50 of ionizing radiation. In conclusion, WT1 overexpression did not protect against p53-mediated apoptosis or ionizing radiation induced cell death. WT1 siRNA increased the radiosensitivity of two human glioma cell lines independently of p53. Anti-WT1 strategies may, therefore, prove useful in improving the response of glioblastoma to radiotherapy, thus potentially improving patient survival.